PMID- 35743148
OWN - NLM
STAT- MEDLINE
DCOM- 20220627
LR  - 20230412
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 12
DP  - 2022 Jun 16
TI  - NMDA and P2X7 Receptors Require Pannexin 1 Activation to Initiate and Maintain 
      Nociceptive Signaling in the Spinal Cord of Neuropathic Rats.
LID - 10.3390/ijms23126705 [doi]
LID - 6705
AB  - Pannexin 1 (Panx1) is involved in the spinal central sensitization process in 
      rats with neuropathic pain, but its interaction with well-known, pain-related, 
      ligand-dependent receptors, such as NMDA receptors (NMDAR) and P2X7 purinoceptors 
      (P2X7R), remains largely unexplored. Here, we studied whether NMDAR- and 
      P2X7R-dependent nociceptive signaling in neuropathic rats require the activation 
      of Panx1 channels to generate spinal central sensitization, as assessed by 
      behavioral (mechanical hyperalgesia) and electrophysiological (C-reflex wind-up 
      potentiation) indexes. Administration of either a selective NMDAR agonist i.t. 
      (NMDA, 2 mM) or a P2X7R agonist (BzATP, 150 muM) significantly increased both the 
      mechanical hyperalgesia and the C-reflex wind-up potentiation, effects that were 
      rapidly reversed (minutes) by i.t. administration of a selective pannexin 1 
      antagonist (10panx peptide, 300 muM), with the scores even reaching values of rats 
      without neuropathy. Accordingly, 300 muM 10panx completely prevented the effects 
      of NMDA and BzATP administered 1 h later, on mechanical hyperalgesia and C-reflex 
      wind-up potentiation. Confocal immunofluorescence imaging revealed coexpression 
      of Panx1 with NeuN protein in intrinsic dorsal horn neurons of neuropathic rats. 
      The results indicate that both NMDAR- and P2X7R-mediated increases in mechanical 
      hyperalgesia and C-reflex wind-up potentiation require neuronal Panx1 channel 
      activation to initiate and maintain nociceptive signaling in neuropathic rats.
FAU - Bravo, David
AU  - Bravo D
AD  - Laboratorio de Neurobiologia, Facultad de Quimica y Biologia, Universidad de 
      Santiago de Chile, Santiago 9170022, Chile.
AD  - Center for the Development of Nanoscience and Nanotechnology (CEDENNA), Santiago 
      9170022, Chile.
FAU - Zepeda-Morales, Katherine
AU  - Zepeda-Morales K
AD  - Laboratorio de Neurobiologia, Facultad de Quimica y Biologia, Universidad de 
      Santiago de Chile, Santiago 9170022, Chile.
FAU - Maturana, Carola J
AU  - Maturana CJ
AUID- ORCID: 0000-0001-8737-300X
AD  - Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA.
FAU - Retamal, Jeffri S
AU  - Retamal JS
AUID- ORCID: 0000-0003-4984-4530
AD  - Laboratorio de Neurobiologia, Facultad de Quimica y Biologia, Universidad de 
      Santiago de Chile, Santiago 9170022, Chile.
AD  - Bluestone Center, New York University, New York, NY 10010, USA.
FAU - Hernandez, Alejandro
AU  - Hernandez A
AD  - Laboratorio de Neurobiologia, Facultad de Quimica y Biologia, Universidad de 
      Santiago de Chile, Santiago 9170022, Chile.
FAU - Pelissier, Teresa
AU  - Pelissier T
AD  - Laboratorio de Neurobiologia, Facultad de Quimica y Biologia, Universidad de 
      Santiago de Chile, Santiago 9170022, Chile.
FAU - Barra, Rafael
AU  - Barra R
AUID- ORCID: 0000-0002-2898-3729
AD  - Centro de Investigacion Biomedica y Aplicada (CIBAP), Escuela de Medicina, 
      Facultad de Ciencias Medicas, Universidad de Santiago de Chile, Santiago 9170022, 
      Chile.
FAU - Saez-Briones, Patricio
AU  - Saez-Briones P
AUID- ORCID: 0000-0002-1491-2639
AD  - Laboratorio de Neurofarmacologia y Comportamiento, Escuela de Medicina, Facultad 
      de Ciencias Medicas, Universidad de Santiago de Chile, Santiago 9170022, Chile.
FAU - Burgos, Hector
AU  - Burgos H
AD  - Escuela de Psicologia, Facultad de Medicina y Ciencias de la Salud, Universidad 
      Mayor, Santiago 7570008, Chile.
FAU - Constandil, Luis
AU  - Constandil L
AUID- ORCID: 0000-0002-2504-0119
AD  - Laboratorio de Neurobiologia, Facultad de Quimica y Biologia, Universidad de 
      Santiago de Chile, Santiago 9170022, Chile.
AD  - Center for the Development of Nanoscience and Nanotechnology (CEDENNA), Santiago 
      9170022, Chile.
LA  - eng
GR  - P40 OD010996/OD/NIH HHS/United States
GR  - AFB180001/Centers of Excellence with Basal/Conicyt financing, CEDENNA/
GR  - 1181622/Fondo Nacional de Desarrollo Cientifico y Tecnologico, FONDECYT/
PT  - Journal Article
DEP - 20220616
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Connexins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Receptors, Purinergic P2X7)
RN  - 0 (pannexin 1, rat)
RN  - 6384-92-5 (N-Methylaspartate)
SB  - IM
MH  - Animals
MH  - Connexins/*metabolism
MH  - *Hyperalgesia/drug therapy/etiology/metabolism
MH  - N-Methylaspartate/metabolism
MH  - Nerve Tissue Proteins/*metabolism
MH  - Nociception
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
MH  - *Receptors, Purinergic P2X7/metabolism
MH  - Spinal Cord/metabolism
PMC - PMC9223805
OTO - NOTNLM
OT  - NMDA receptor
OT  - P2X7 receptor
OT  - neuropathic pain
OT  - pannexin 1
OT  - wind-up
COIS- The authors declare no conflict of interest.
EDAT- 2022/06/25 06:00
MHDA- 2022/06/28 06:00
PMCR- 2022/06/16
CRDT- 2022/06/24 01:22
PHST- 2022/05/27 00:00 [received]
PHST- 2022/06/13 00:00 [revised]
PHST- 2022/06/14 00:00 [accepted]
PHST- 2022/06/24 01:22 [entrez]
PHST- 2022/06/25 06:00 [pubmed]
PHST- 2022/06/28 06:00 [medline]
PHST- 2022/06/16 00:00 [pmc-release]
AID - ijms23126705 [pii]
AID - ijms-23-06705 [pii]
AID - 10.3390/ijms23126705 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Jun 16;23(12):6705. doi: 10.3390/ijms23126705.